CA2558581A1 - Nouvelle methode de synthese d'un acide nucleique sans protection des groupes fonctionnels des bases - Google Patents
Nouvelle methode de synthese d'un acide nucleique sans protection des groupes fonctionnels des bases Download PDFInfo
- Publication number
- CA2558581A1 CA2558581A1 CA002558581A CA2558581A CA2558581A1 CA 2558581 A1 CA2558581 A1 CA 2558581A1 CA 002558581 A CA002558581 A CA 002558581A CA 2558581 A CA2558581 A CA 2558581A CA 2558581 A1 CA2558581 A1 CA 2558581A1
- Authority
- CA
- Canada
- Prior art keywords
- synthesis
- hobt
- nucleic acid
- activator
- acid catalyst
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 16
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 16
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 12
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 12
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 12
- 239000012190 activator Substances 0.000 claims abstract description 20
- 239000003377 acid catalyst Substances 0.000 claims abstract description 13
- 150000008300 phosphoramidites Chemical class 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 13
- 239000007790 solid phase Substances 0.000 claims description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- DGIBHCWBCOAPDN-UHFFFAOYSA-N 1-hydroxy-6-(trifluoromethyl)benzotriazole Chemical group C1=C(C(F)(F)F)C=C2N(O)N=NC2=C1 DGIBHCWBCOAPDN-UHFFFAOYSA-N 0.000 claims description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 6
- 150000002989 phenols Chemical class 0.000 claims description 6
- DZCRSVQAXDNLEY-UHFFFAOYSA-N 1-ethylsulfanyltetrazole Chemical compound CCSN1C=NN=N1 DZCRSVQAXDNLEY-UHFFFAOYSA-N 0.000 claims description 3
- DDUUDXXWQISHKG-UHFFFAOYSA-N 1-hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole Chemical compound C1=C(C(F)(F)F)C=C2N(O)N=NC2=C1[N+]([O-])=O DDUUDXXWQISHKG-UHFFFAOYSA-N 0.000 claims description 3
- HZPVTKPGROKWRL-UHFFFAOYSA-N 1-hydroxy-6-nitrobenzotriazole Chemical compound C1=C([N+]([O-])=O)C=C2N(O)N=NC2=C1 HZPVTKPGROKWRL-UHFFFAOYSA-N 0.000 claims description 3
- XGDRLCRGKUCBQL-UHFFFAOYSA-N 1h-imidazole-4,5-dicarbonitrile Chemical compound N#CC=1N=CNC=1C#N XGDRLCRGKUCBQL-UHFFFAOYSA-N 0.000 claims description 3
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 claims description 3
- FTVOPKROFUTOKY-UHFFFAOYSA-N 4-hydroxybenzene-1,2-dicarbonitrile Chemical compound OC1=CC=C(C#N)C(C#N)=C1 FTVOPKROFUTOKY-UHFFFAOYSA-N 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- JNJFONBBNLVENC-UHFFFAOYSA-N 1h-imidazole;trifluoromethanesulfonic acid Chemical compound C1=CNC=N1.OS(=O)(=O)C(F)(F)F JNJFONBBNLVENC-UHFFFAOYSA-N 0.000 claims 2
- XZEDEVRSUANQEM-UHFFFAOYSA-N 2-nitro-4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O XZEDEVRSUANQEM-UHFFFAOYSA-N 0.000 claims 2
- DQMFCPJOEBYZTC-UHFFFAOYSA-N 1-hydroxybenzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2O DQMFCPJOEBYZTC-UHFFFAOYSA-N 0.000 claims 1
- 238000010532 solid phase synthesis reaction Methods 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000007796 conventional method Methods 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 2
- 239000002773 nucleotide Substances 0.000 abstract 2
- 125000003729 nucleotide group Chemical group 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000005406 washing Methods 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000000018 DNA microarray Methods 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DRHQKJKROQSOGW-BBZRCZKMSA-N [(2r,3s,5r)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methyl [(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)[C@@H](O)C1 DRHQKJKROQSOGW-BBZRCZKMSA-N 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004-056707 | 2004-03-01 | ||
| JP2004056707 | 2004-03-01 | ||
| PCT/JP2005/003053 WO2005082923A1 (fr) | 2004-03-01 | 2005-02-24 | Nouveau procédé de synthèse d'acide nucléique sans protéger les bases des nucléotides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2558581A1 true CA2558581A1 (fr) | 2005-09-09 |
Family
ID=34908936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002558581A Abandoned CA2558581A1 (fr) | 2004-03-01 | 2005-02-24 | Nouvelle methode de synthese d'un acide nucleique sans protection des groupes fonctionnels des bases |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7807821B1 (fr) |
| EP (1) | EP1721908A4 (fr) |
| JP (1) | JPWO2005082923A1 (fr) |
| CA (1) | CA2558581A1 (fr) |
| WO (1) | WO2005082923A1 (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636368A (zh) * | 2007-03-09 | 2010-01-27 | 通用电气健康护理有限公司 | 分离方法 |
| JP5438922B2 (ja) | 2008-06-25 | 2014-03-12 | 日東電工株式会社 | 核酸の製造方法 |
| BR112015005389B1 (pt) | 2012-09-13 | 2022-10-18 | Indiana University Research And Technology Corporation | Molécula de ácido nucleico recombinante, proteína de substrato modificada de uma protease específica de patógeno de planta expressa através do patógeno de planta, vetor, e método para proteger uma planta da infecção por um patógeno de planta que secreta pelo menos uma protease específica |
| US20150259743A1 (en) | 2013-12-31 | 2015-09-17 | Roche Nimblegen, Inc. | Methods of assessing epigenetic regulation of genome function via dna methylation status and systems and kits therefor |
| BR112020016306A2 (pt) | 2018-02-12 | 2020-12-15 | Curators Of The University Of Missouri | Gene (saur) suprarregulado pequeno de auxina para o melhoramento da arquitetura do sistema radicular da planta, tolerância ao encharcamento, resistência à seca, e rendimento |
| JP7298866B2 (ja) * | 2019-02-25 | 2023-06-27 | 国立大学法人東京工業大学 | 核酸合成用固相担体及びそれを用いた核酸の製造方法 |
| JP2022177332A (ja) * | 2019-10-24 | 2022-12-01 | 日東電工株式会社 | オリゴヌクレオチドを製造する方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6251695A (ja) * | 1985-08-29 | 1987-03-06 | Yuki Gosei Yakuhin Kogyo Kk | ホスホロアミダイト類の合成法 |
| JPH1180185A (ja) * | 1997-09-05 | 1999-03-26 | Res Dev Corp Of Japan | オリゴヌクレオチドの化学合成法 |
| JP4184718B2 (ja) * | 1999-12-06 | 2008-11-19 | 富士フイルム株式会社 | 反応性固相担体の製造方法 |
| US20010008765A1 (en) | 1999-12-06 | 2001-07-19 | Fuji Photo Film Co., Ltd. | DNA chip and reactive solid carrier |
| US20030096257A1 (en) | 1999-12-06 | 2003-05-22 | Hiroshi Shinoki | DNA chip and reactive solid carrier |
| JP2003002895A (ja) * | 2001-05-30 | 2003-01-08 | Tokyo Inst Of Technol | 核酸の合成法 |
| JP2004099532A (ja) * | 2002-09-10 | 2004-04-02 | Sigma Genosys Japan Kk | オリゴヌクレオチド合成法 |
-
2005
- 2005-02-24 EP EP05710654A patent/EP1721908A4/fr not_active Withdrawn
- 2005-02-24 US US10/591,172 patent/US7807821B1/en not_active Expired - Fee Related
- 2005-02-24 CA CA002558581A patent/CA2558581A1/fr not_active Abandoned
- 2005-02-24 JP JP2006510452A patent/JPWO2005082923A1/ja active Pending
- 2005-02-24 WO PCT/JP2005/003053 patent/WO2005082923A1/fr active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2005082923A1 (ja) | 2007-11-15 |
| WO2005082923A1 (fr) | 2005-09-09 |
| US7807821B1 (en) | 2010-10-05 |
| EP1721908A1 (fr) | 2006-11-15 |
| EP1721908A4 (fr) | 2009-12-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130402 |